title: All-trans retinoic acid regulates the expression of apolipoprotein E in rats with glomerulosclerosis induced by Adriamycin.
abstract: Apolipoprotein E (apoE) is an important plasma protein in cholesterol homeostasis and plays a key role in the progression of glomerulosclerosis (GS). We conducted this investigation to explore whether all-trans retinoic acid (ATRA) could regulate the apoE expression in the pathological process of GS. 120 Wistar rats were divided into three groups at random: sham operation group (SHO), glomerulosclerosis model group without treatment (GS), GS model group treated with ATRA (GA); n=40, respectively. The disease of GS in rat was established by uninephrectomy and adriamycin (5mg/kg) injection. At the end of 9 and 13 weeks, 20 rats in each group were killed and the relevant samples were collected. 24-hour urine total protein (24UTP), 24-hour urine excretion for albumin (24Ualb), serum total protein (TP) and serum albumin (Alb), blood urea nitrogen (BUN), serum creatinine (Scr), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), serum and urine apoE and glomerulosclerosis index (GSI) were measured. The protein expressions of collagen IV (Col-IV), fibronectin (FN) and apoE in glomeruli were determined by immunohistochemistry. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to detect the expression of apoE mRNA in kidney. TP and Alb in GA group in 9/13-week were increased than those of GS group, however, the differences were not statistically significant. Compared with group GS at 9/13 weeks, values of 24UTP, 24Ualb, BUN, Scr, TC, TG, HDL, LDL, serum and urine apoE, and GSI in GA group that were significantly reduced, and protein expressions of Col-IV, FN and apoE in glomeruli and expression of apoE mRNA in renal tissue were significantly down-regulated by ATRA (P<0.01). In conclusion, ATRA can regulate the expression of apoE, reduce the accumulation of extracellular matrix (ECM) and step down the progression of GS.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University, NanNing, China.
authors.forename: Tian-Biao
authors.initials: TB
authors.lastname: Zhou
authors.forename: Yuan-Han
authors.initials: YH
authors.lastname: Qin
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Lei
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Su
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Zhao
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Huang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001057:Apolipoproteins E; D024141:Collagen Type IV; D005353:Fibronectins; D012333:RNA, Messenger; D014212:Tretinoin; D004317:Doxorubicin